Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives from new 5-aminopyrazoles

• Published in: European journal of medicinal chemistry 2013-06, Vol.64, p.464-476
• Main Authors: Al-Adiwish, Wedad M., Tahir, M.I.M., Siti-Noor-Adnalizawati, A., Hashim, Siti Farah, Ibrahim, Nazlina, Yaacob, W.A.
• Format: Article
• Language: English
• Subjects: 5-Aminopyrazoles; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Bacteria - drug effects; Cell Survival - drug effects; Cercopithecus aethiops; Crystallography, X-Ray; Cytotoxicity; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazolo[1,5-a]pyrimidines; Pyrazolo[5,1-c][1,2,4]triazines; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Triazines - chemical synthesis; Triazines - chemistry; Triazines - pharmacology; Vero Cells; α,α-Dicyanoketene-S,S- and N,S-acetals
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.04.029

New 5-aminopyrazoles 2a–c were prepared in high yields from the reaction of known α,α-dicyanoketene-N,S-acetals 1a–c with hydrazine hydrate under reflux in ethanol. These compounds were utilized as intermediates to synthesize pyrazolo[1,5-a]-pyrimidines 3a–c, 4a–d, 5a–c, and 6a–c, as well as pyrazolo[5,1-c][1,2,4]triazines 7a–c and 8a–c, by the reaction of 2-[bis(methylthio)methylene]malononitrile, α,α-dicyanoketene-N,S-acetals 1a–b, acetylacetone, acetoacetanilide as well as acetylacetone, and malononitrile, respectively. Furthermore, cyclization of 2a–c with pentan-2,5-dione yielded the corresponding 5-pyrrolylpyrazoles 9a–c. Moreover, fusion of 2a–c with acetic anhydride resulted in the corresponding 1-acetyl-1H-pyrazoles 10a–c. The antibacterial activity and cytotoxicity against Vero cells of several selected compounds are also reported. [Display omitted] •New 5-aminopyrazoles, pyrazolo[1,5-a]-pyrimidines and pyrazolo[5,1-c][1,2,4]triazines have been synthesized.•Their antibacterial activity and cytotoxicity have been tested.•Elemental analysis and spectroscopic characterization of all new compounds.